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Thyrotropin-Secreting Pituitary Adenoma: a Structured Review of 535 Adult Cases

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Thyrotropin-Secreting Pituitary Adenoma: a Structured Review of 535 Adult Cases 2 185 C De Herdt and others Thyrotropin-stimulating 185:2 R65–R74 Review pituitary adenoma ENDOCRINE TUMOURS Thyrotropin-secreting pituitary adenoma: a structured review of 535 adult cases Carlien De Herdt1, Eva Philipse1,2 and Christophe De Block1,3 1Department of Endocrinology-Diabetology-Metabolism, Antwerp University Hospital, Antwerp, Belgium, Correspondence 2Department of Endocrinology-Diabetology, Heilig Hart Hospital Lier, Antwerp, Belgium, and 3University of Antwerp, should be addressed Faculty of Medicine and Health Sciences, Antwerp, Belgium to C De Block Email [email protected] Abstract Background and aims: Thyrotropin-secreting pituitary adenomas (TSHomas) are a rare entity, occurring in one per million people. We performed a systematic review of 535 adult cases summarizing the clinical, biochemical, hormonal and radiological characteristics of TSHoma. Furthermore, we discussed the current guidelines for diagnosis and treatment. Methods: A structured research was conducted using Pubmed and Web of Science with the following MeSH terms: 'thyrotropin secreting pituitary adenoma' OR 'TSHoma' OR 'thyrotropinoma.' Results: Our analysis included 535 cases originating from 18 case series, 5 cohort studies and 91 case reports. The mean age at diagnosis was 46 years. At presentation, 75% had symptoms of hyperthyroidism, 55.5% presented with a goitre and 24.9% had visual field defects. The median TSH at diagnosis was 5.16 (3.20–7.43) mU/L with a mean FT4 of 41.5 ± 15.3 pmol/L. The majority (76.9%) of the TSHomas were macroadenoma. Plurihormonality was seen in 37.4% of the adenoma with a higher incidence in macroadenoma. Surgical resection of the adenoma was performed in 87.7% of patients of which 33.5% had residual pituitary adenoma. Post-operative treatment with a somatostatin analogue (SSA) European Journal of Endocrinology led to a stable disease in 81.3% of the cases with residual tumour. We noticed a significant correlation between the diameter of the adenoma and residual pituitary adenoma (r = 0.490, P < 0.001). However, in patients preoperatively treated with an SSA, this correlation was absent. Conclusion: TSHomas are a rare cause of hyperthyroidism and are frequently misdiagnosed. Based on our structured analysis of case series, cohort studies and case reports, we conclude that the majority of TSHomas are macroadenoma being diagnosed in the fifth to sixth decade of life and presenting with symptoms of hyperthyroidism. Plurihormonalitiy is observed in one-third of TSHomas. Treatment consists of neurosurgical resection and SSA in case of surgical failure. European Journal of Endocrinology (2021) 185, R65–R74 Introduction Hyperthyroidism is mainly due to autoimmune thyroid rarest form of pituitary adenoma accounting for 3% of all disorders, a toxic thyroid nodule or goitre and is rarely caused pituitary tumours and are frequently misdiagnosed, leading by a thyrotropin-secreting pituitary adenoma (TSHoma), a to an inappropriate treatment such as thyroidectomy (1, pituitary tumour characterized by an autonomous secretion 2, 3, 4). In 2013, the first European guidelines concerning of thyroid-stimulating hormone (TSH) (1). TSHomas are the the diagnosis and treatment of TSHomas were issued by https://eje.bioscientifica.com © 2021 European Society of Endocrinology Published by Bioscientifica Ltd. https://doi.org/10.1530/EJE-21-0162 Printed in Great Britain Downloaded from Bioscientifica.com at 10/02/2021 11:27:46PM via free access -21-0162 Review C De Herdt and others Thyrotropin-stimulating 185:2 R66 pituitary adenoma the European Thyroid Association and updated in 2019 (1, 3). Here, we provide a structured analysis of the clinical, biochemical, hormonal and radiological presentation of previously published cohort studies, case series and case reports. Because we assessed individual data of case reports, we were able to describe the patients in detail, analysing clinical and hormonal characteristics not described in the previous reviews. We also describe rare cases of TSHoma with concomitant Graves’ disease or thyroid carcinoma and TSHoma complicated by a thyroid storm. Methods Search strategy A structured search was conducted using Pubmed and Web of Science with the following MeSH terms: 'thyrotropin secreting pituitary adenoma' OR 'TSHoma' OR 'thyrotropinoma.' All case reports, case series and cohort studies published in English between 1991 and October 2020 were considered. Articles published before 1991 frequently missed important information, as listed subsequently, and were, therefore, not included. The results of the search process are summarized in a flowchart (Fig. 1). Exclusion criteria were as follows: (1) diagnosis other than TSHoma, (2) missing more than six of the following eight characteristics: age at diagnosis, clinical presentation, European Journal of Endocrinology presence/absence of goitre, visual field assessment, level of TSH and free T4 (FT4), the diameter of the Figure 1 Flowchart of the literature study. adenoma, or treatment modalities, Descriptive statistics were used to analyse population (3) age under 16 years as their reference ranges of thyroid characteristics. Distributions of continuous data were hormones and TSH differ from those of adults. tested for normality by the Kolmogorov–Smirnov test Diagnosis of TSHoma had to be confirmed by dynamic and Q–Q plot. To investigate a correlation between testing or TSH had to be unsuppressed in a hyperthyroid two variables, Spearman’s correlation was used. Study patient with a pituitary adenoma with positive population characteristics and laboratory measurements immunohistochemistry to be included in the systematic were presented as mean values ± s.d. if normally distributed review. We included 107 articles in this review consisting and as median with lower and upper quartile when not of 91 case reports, 18 case series (including ≥ 5 cases) normally distributed. and 5 cohort studies resulting in a total of 535 cases. The case series and cohort studies included in the review are summarized in the supplemental table (see section on Results Supplementary materials at the end of the article). General characteristics The female to male ratio for TSHoma was 1.07. The mean Statistical analysis age at diagnosis was 46 ± 6 years in the case series and Statistical analysis was performed using the statistical 45 ± 14 years in the case reports (Table 1). Symptoms and package SPSS (version 26; Armonk, NY, IBM Corp). signs of hyperthyroidism were present in 75% of patients https://eje.bioscientifica.com Downloaded from Bioscientifica.com at 10/02/2021 11:27:46PM via free access Review C De Herdt and others Thyrotropin-stimulating 185:2 R67 pituitary adenoma Table 1 Characteristics of the patients at the time of diagnosis and treatment. The mean values of the study population characteristics and laboratory measurements of the case series and cohort studies are presented as mean values ± S.D. or as n (%) if normally distributed and as median with lower and upper quartile when not normally distributed. Case series and cohort studies Not reported Case reports Not reported All data Reported cases, n 444 91 535 (A) Demographics Males 219 (49.3) 40 (44.0) 259 (48.4) Age (years) 46 ± 6 45 ± 14 (B) Clinical presentation Hyperthyroidism 302 (75.3) 43 (9.7) 64 (73.6) 4 (4.4) 366 (75.0) AF and/or cardiac failure 25 (9.5) 181 (40.8) 14 (15.9) 3 (3.3) 39 (11.1) Goitre 109 (52.7) 237 (53.4) 46 (63.9) 19 (20.9) 155 (55.5) Visual field defect 86 (25.2) 103 (23.2) 14 (23.3) 31 (34.1) 100 (24.9) (C) Biochemical presentation TSH† (mU/L) 6.75 (4.02–11.90) 5.16 (3.20–7.43)* FT4 (pmol/L) 35.7 ± 8.5 41.5 ± 15.3* TRAbs 4 (4.4) (D) Adenoma Macroadenoma 334 (77.9) 15 (3.4) 62 (78.5) 7 (7.7) 396 (76.9) Diameter (mm) 21.5 ± 7.9 19.8 ± 13.6 Ectopic tumour 5 (5.5) (E) Co-secretion Plurihormonal 140 (35.9) 54 (12.2) 34 (49.3) 22 (24.2) 174 (37.9) Co-secretion of GH 78 (55.7) 22 (64.7) 100 (57.5) Co-secretion of prolactin 56 (40.0) 16 (47.1) 72 (41.4) Co-secretion of ACTH 0 Co-secretion of FSH 9 (26.5) Co-secretion of LH 3 (8.8) (F) Treatment Transsphenoidal resection 396 (89.2) 80 (87.9) 469 (89.0) SSA preoperatively 143 (36.1) 26 (32.5) 169 (36.0) SSA post-operatively 62 (15.7) 23(28.8) 85 (18.1) Radiotherapy 74 (16.7) 7 (7.7) 81 (15.1) SSA monotherapy 8 (8.8) European Journal of Endocrinology †Values presented as median (lower and upper quartile); *exclusion of (10) cases who underwent a thyroidectomy before diagnosis of TSHoma. ACTH, adrenocorticotropic hormone; AF, atrial fibrillation; FSH, follicle-stimulating hormone; LH, luteinizing hormone; TRAbs, thyroid-stimulating hormone receptor antibodies. and 55.5% had a goitre. In half of the cases, the presence adenomas (62.1%) were pure TSHomas. Co-secretion with of a goitre was not assessed/reported. Atrial fibrillation or growth hormone (GH) was seen in 57.5% and co-secretion heart failure were seen in 11.1% of the cases. Visual field with prolactin was seen in 41.4% of the plurihormonal defects were noticed in 100 patients (24.9%). adenoma. In the case reports, co-secretion of follicle- The median TSH at diagnosis was 6.75 (4.02–11.90) stimulating hormone (FSH) and luteinizing hormone mU/L in the case series and 5.16 (3.20–7.43) mU/L in (LH) were reported in 26.5 and 8.8% of the plurihormonal the case reports whereas FT4 averaged 35.7 ± 8.5 and adenoma, respectively. No case had co-secretion with 41.5 ± 15.3 pmol/L, respectively. Ten cases underwent total adrenocorticotropic hormone (ACTH). Plurihormonality thyroidectomy before the diagnosis of TSHoma and had a was more frequent in macroadenoma (51.1%) than median TSH of 3.75 (2.16–25.3) mU/L.
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